Glomerular diseases: Glomerulonephritis

Picture: “Photomicrograph of the renal biopsy showing prominent fibrocellular crescent formation and moderate mesangial proliferation in a glomerulus. Hematoxylin and eosin stain. “From Journal of Medical Case Reports. License: CC BY 2.0

introduction

Picture: “Light microscopic cross-sectional view of the renal cortex” of a rolling robot. License: CC BY-SA 3.0

Structure of the filter membrane of the glomeruli

Damage to the kidney can affect all anatomical structures. This article is concerned with the damage to the kidney corpuscles, too glomeruli called. In order to better understand the individual diseases with their clinical features, a look into the anatomical and physiological structure of the glomeruli helps. The structure of the filter membrane is three-layered and consists of:

Fenestrated capillary endothelium,
Glomerular basement membrane and
Visceral sheet of Bowman’s capsule.

The endothelium is negatively charged proteoglycans and glycosaminoglycans occupied. The glomerular basement membrane forms the connecting layer between capillaries and Bowman’s capsule and consists of a dense meshwork, which forms a fine mechanical filter structure. Like the capillary endothelium, it is filled with proteoglycans and therefore has a negative charge. The cells of the visceral sheet of Bowman’s capsule possess the so-called podocytes, whose extensions also form a meshwork.

Through the narrow mesh large molecules or even cells do not get into the primary urine. At the same time, the negative charge prevents the filtration of anions, such. B. the albumin.

Picture: “A renal; B Main piece; C Centerpiece; D Juxtaglomerular apparatus1 basement membrane; 2 Bowman’s capsule, parietal leaf; 3 Bowman’s capsule, visceral sheet; 3a Podozytenfüsschen; 3b podocyte;4 Lumen of Bowman’s capsule (urinary tract); 5a Mesangium – intraglomerular mesangial cells; 5b Mesangium – extraglomerular mesangial cells; 6 Juxtaglomerular cells; 7 Macula densa; 8th Myocytes (muscle cells of the arteriolar wall); 9 Arteriola afferens;10 glomerular capillaries; 11 Arteriola efferens “by M.Komorniczak. License: CC BY-SA 3.0

Damage to the filter membrane of the glomeruli

If this filtration layer is damaged, these parts of the body (cells, albumin, macromolecules) enter the body primary urine and are eliminated. With a further disintegration of the glomeruli arises over time an inability to urinate – it results in a renal insufficiency.

Glomerulonephritis versus glomerulopathy

This injury can have different causes. Important is the distinction of glomerulonephritis from non-inflammatory glomerulopathies. The description of glomerulonephritis should be the focus of this article. Explanations of non-inflammatory causes such as mechanical (eg. hypertensive nephropathy), metabolic (e.g.. diabetic nephropathy) or vascular (e.g.. thrombotic microangiopathy) Factors can be found in the contributions of the respective diseases.

diagnostics

Investigation of glomerular diseases

Different techniques give conclusions about the type and location of damage in the urine-producing system. At this point in particular the methods are to be presented, which show a damage of the Glomeruli:

hematuria: The examination of the urine sediment can be between hematuria, hemoglobinuria and myoglobinuria differ. From one microhematuria one speaks off > 5 erythrocytes / μl urine, with no visible red coloration of urine. As soon as you recognize a red color, it is a gross hematuria. Erythrocytes can also look dysmorphic in the sediment. This change in shape occurs when the cells migrate through the tubule system and are exposed to the osmotic stresses. An example is the acanthocytes, which have a prickly shape

proteinuria: Normally only small amounts of protein appear in the excreted urine. From a protein excretion > 150 mg / d is called a proteinuria. The amount of pathological protein excretion can give clues to the cause of the disease.

amount of protein	protein type	Possible Cause
20-200 mg / l	albumin	Microalbuminuria as an expression of early nephropathy, e.g. In the context of hypertensive or diabetic disorders
up to 1.5 g / d	Small Molecule Proteins:

Large Molecular Proteins:

tubulopathy

glomerulopathy

1.5 g / d – 3.0 g / d Small and large molecular proteins Chronic glomerulonephritis, transplant kidney > 3.0 g / d Large Molecular Proteins Nephrotic syndrome

(after: Herold G. and co-workers: Internal Medicine, 2014)

glucosuria: Adults do not divorce more than about 60 mg per day glucose per day off. A pathologically increased urine glucose occurs when the glucose threshold (about 160 – 180 mg / dl). This happens, for example, in the context of diabetes mellitus. Glucosuria in normal blood glucose can occur during pregnancy or during kidney tubular diseases.

cylinder: Cylinders are created in tubules and thus show one renal Emergence. The often found hyaline Cylinders are found in healthy individuals, but are also elevated in the context of glomerular diseases and thus relatively unspecific. red blood cell casts are formed in a glomerulonephritis, Leukozytenzylinder during a (chronic) pyelonephritis.

immunology: The search for different antibodies helps in the etiological grouping z. B. a glomerulonephritis. The individual antibodies are noted in the respective disease. In terms of economic approaches, not all antibodies should be initially determined in suspected glomerulonephritis.

imaging: The Color duplex sonography As a non-invasive procedure, there are many indications for renal assessment. over CT and MRI Representations can be obtained further structural information. Often these procedures are with angiographic Methods combined.

histologyThe ultimate confirmation of the diagnosis of glomerulonephritis typing is (only) achieved by the renal biopsy! In particular, if a prompt and dramatic clinic requires prompt, adequate treatment, kidney biopsy is often the life-saving method of choice.

glomerulonephritis

Definition of glomerulonephritis

A nonbacterial, immune-mediated Inflammation of the renal corpuscles is called glomerulonephritis. The genesis of the inflammation is manifold. It can be primary from secondary Different forms of secondary forms, the secondary forms arise in the context of various systemic diseases, while the primary occur without systemic disease.

Depending on the pathogenesis, patients with glomerulonephritides also present with different symptoms. While some forms are due to an early surge in retention parameters stand out, is in other forms more of an unphysiological filter function in the foreground.

Pathomechanisms of glomerulonephritis

Various immune reactions can be observed in glomerulonephritis. The different pathogenesis depends on the causative disease and sometimes determines the clinical course:

Anti-GBM antibody-mediated glomerulonephritis: Antibodies of the IgG type to the Goodpasture antigen of the basement membrane cause an antibody-mediated inflammatory response. The Goodpasture antigen additionally occurs in the alveolar basement membrane.
Immune complex-mediated glomerulonephritis: Immune complexes formed as part of infections or autoimmune diseases deposit on the capillary wall.
ANCA-associated glomerulonephritis: Anti-neutrophil cytoplasmic antibodies (ANCA) interact with neutrophil granule components to cause glomerular damage

All immune mechanisms start a complex, proinflammatory immune cascade with subsequent inflammatory reaction. This inflammatory reaction ultimately leads to damage to the glomerular capillary wall. It comes to hemorrhage in the Bowman’s capsule and thus in the primary urine.

The kidney body then becomes necrotic and loses its function. The more glomeruli affected, the more likely there is a detectable loss of renal total function with decreasing glomerular filtration rate and increase in the retention parameters.

Forms of glomerulonephritis

To work up the Glomerulonephritiden didactic divide different textbooks primary and secondary To shape. This subdivision succeeds in some forms, in others it often causes confusion: many inflammations arise in both ways and some syndromes unite “primary” and “secondary” forms. This article dispenses with the rigid classification into primary and secondary and deals with the different diseases due to common clinical pictures:

Localized glomerulonephritis
Rapidly progressive glomerulonephritides
Glomerulonephritides (and other diseases) leading to nephrotic syndrome

Localized glomerulonephrites:

Various diseases trigger a bacterial inflammatory reaction especially of the renal corpuscles. This group includes, for example, the M. Berger (IgA nephropathy), hereditary glomerulonephritis and the acute, postinfectious glomerulonephritis.

Even minimal-change glomerulonephritis, membranous glomerulonephritis, membranoproliferative glomerulonephritis and focal segmental glomerulonephritis can idiopathically affect only the glomeruli, but they often develop in the context of systemic diseases. Characteristically these 4 diseases lead to nephrotic syndrome and are described there in more detail.

Immunoglobulin A nephropathy (M. Berger)

Definition, epidemiology and etiology of IgA nephropathy

IgA nephropathy is the common primary glomerulonephritis worldwide and affects mainly younger patients. The etiology is mostly idiopathic, however, as the name suggests, IgA-associated diseases can also trigger a M. Berger. This disease group includes, for example, the sprue, the Crohn’s disease, the Schönlein-Henoch purpura, rheumatoid arthritis, systemic lupus erythematosus or IgA gammopathies. Typically, IgA nephropathy is nonspecific infection ahead of the upper respiratory tract.

Pathophysiology and clinic of IgA nephropathy

The IgA immune complexes store in the mesangial of the glomeruli and lead to an inflammatory reaction microhematuria. Rarely can other depositional patterns arise that result in rapid progressive glomerulonephritis (subendothelial deposits) or a nephrotic syndrome (subepithelial deposits).

Typically, those affected are asymptomatic microhematuria in front. Partially it happens hypertension and rarely too flank pain. In case of rapid progressive glomerulonephritis or nephrotic syndrome, another clinic exists accordingly (see above)..

The diagnostic evidence is ultimately by a renal biopsy achieved with representation of IgA complexes.

Therapy and prognosis of IgA nephropathy

In general, there is a good prognosis with regular IgA nephropathy Spontaneous remissions. However, depending on the extent of glomerular damage, the risk of progressive loss of renal function with imminent end stage renal failure increases.

The therapy depends on the symptoms and the proteinuria:

Proteinuria 1g / d: This is definitely a therapy with ACE inhibitors instead.
proteinuria > 1g / d and increasing renal insufficiency: There is an attempt to immunological processes using glucocorticosteroids >Hereditary glomerulonephrites

There are several familial glomerulonephritides, which are characterized by a (often asymptomatic) microhematuria notice. With progressive persistence, it comes to a proteinuria and ultimately increasing renal insufficiency.

Therapeutically, there are usually no causal therapeutic options, so in end-stage renal failure transplantation the only option represents. The following diseases of this group can be remembered:

Benign hematuria: syndrome of the thin basement membrane
Alport Syndrome: Hereditary Nephritis

Acute postinfectious glomerulonephritis

In particular, children in countries with less well-equipped health systems are affected by acute post-infectious glomerulonephritis. In Germany, the disease has become rare overall.

Etiology and pathophysiology of acute postinfectious glomerulonephritis

From the name can be deduced that following a infection an (immune complex) nephrite occurs. Especially beta-hemolytic streptococci Group A are responsible for subsequent immunological diseases (rheumatic fever, chorea minor). It comes to endocapillary, proliferative glomerulonephritis by antibody formation against the glomerular structures.

Clinic and diagnosis of acute postinfectious glomerulonephritis

Anamnestisch should one streptococcal infection (pharyngitis, erysipelas, tonsillitis, impetigo, etc.). After this complaining, 50% of sufferers typically report renewed illness. These can be nonspecific (“grippal”), or due to hematuria, hypertension and edema (= Volhard Trias) being shaped. The edema can be multiple and lead to dyspnea or epilepsy. The other 50% of cases are asymptomatic and are discovered by chance.

Fortunately relatively seldom, very rapid glomerulonephritis (= rapid progressive glomerulonephritis, RPGN) develops, leading to a dramatic decrease in renal function with imminent renal insufficiency and high lethality.

Etiological types of RPGN

With about 10% is the Type 1 (Anti-GBM RPGN) the rarest variant: Here it comes to antibody formation against the Goodpasture antigen of the basement membrane. Since this antigen is also part of the alveolar basement membrane, serious damage to the kidney and lungs with hemoptysis develops. The disease often affects younger men.
Of the Type 2 (immune complex RPGN) occurs in 40% of cases: In this case, immune complexes deposit on the basal membrane. These immune complexes can be produced by postinfection or by underlying diseases that produce antibodies (for example, SLE, Schönlein-Henoch purpura).
With 50% most often comes Type 3 (ANCA-associated RPGN) before: This is the cause of ANCA-associated vasculitis. There are no histological deposits. The antibodies are directed against enzymes (e.g., myeloperoxidase in pANCA or antiprotease 3 in cANCA). This antibody production is based, for example, on granulomatosis with polyangiitis (M. Wegener) or microscopic polyangiitis. A Churg-Strauss syndrome is also possible.

Clinic and diagnostics of the RPGN

The victims are severely beaten and pale. Often a hypertension is detectable. A strong proteinuria with appropriate clinic (s.u.) Can arise, but usually finds one nephritic Sediment. On pulmonary Complaints must be respected. In addition to signs of inflammation, rapidly increasing retention parameters can be ascertained.

The different ones antibody or immune complexes can be found in peripheral blood. The well-founded suspicion of RPGN forces renal biopsy. Histopathologisch exists one extracapillary, proliferating Inflammatory reaction with so-called Crescent Education glomeruli.

Image: “Fine tissue section of a RPGN” by KGH. License: CC BY-SA 3.0

Therapy and prognosis of RPGN

The therapy depends on the underlying cause and severity of the disease. In principle one can consider the use of glucocorticoids in high dosage (1g / day i.v.) and cyclophosphamide notice.

At the Goodpasture’s syndrome will be additionally one plasmapheresis used for 2-3 weeks to eliminate the antibodies. After cessation of glucocorticoid and Cyclophosphamidtherapie done here the aftertreatment azathioprine over 6-12 months.

Type 2 and Type 3 The RPGN are being treated longer and more regularly. These forms can cause recurrences! If treatment is given early, improvement and recovery of renal function may occur in more than half of the cases.

Glomerulonephritides (and other diseases) leading to nephrotic syndrome

Definition of nephrotic syndrome

The nephrotic syndrome is defined by the findings constellation:

Great proteinuria > 3 g / day
hypoproteinemia
Hypoalbuminemia-related edema
Hyperlipoproteinemia (especially of cholesterol and triglycerides)

Pathophysiology of the nephrotic syndrome

The nephrotic syndrome is disturbed glomerular filtration barrier which causes the glomerulus to become abnormally permeable. The filter is thus no longer selective, whereby the glomerular perfusion itself is not disturbed. This results in a non-physiologically large amount of ultrafiltered, large molecular weight proteins, which otherwise would not otherwise enter the tubule system and for which it is therefore not suitable Rückresorptionssystem gives.

Causes: What is behind a nephrotic syndrome

A number of glomerulonephritides can be the cause of disturbed filtration. Two forms should be remembered, they are the most common and are regularly checked:

Minimal change glomerulonephritis: Glomerular minimal lesions, which can only be visualized by electron microscopy, are the most common cause of childhood nephrotic syndrome (> 90% of the cases). It comes here either idiopathic or in the context of malignant diseases, NSAIDs, allergies or immunizations (vaccinations!) To a diffuse damage of podocytes.
Membranous glomerulonephritis: This is the most common cause in adulthood and is caused by immune and complement complex formation. These complexes arise either idiopathic or in the context of infections (hepatitis B, HIV, syphilis, malaria), autoimmune diseases, malignancies or pharmaceuticals. Histologically, deposited complexes are found along the glomerular basement membrane.

In addition to these two main forms can also membranoproliferative glomerulonephritis or the focal segmental glomerulonephritis be the cause of a nephrotic syndrome.

The clinical symptoms of nephrotic syndrome

The complaints depend on the ability of the body to compensate. If there is a mild dysfunction, the increased synthesis efficiency of the liver compensates for protein losses. So there is one asymptomatic proteinuria in front. If the filter dysfunction is too large, results in different protein losses, which explain directly the clinical symptoms and thus are easy to remember:

immunoglobulin loss: There is an increased susceptibility to infection.
Antithrombin III Loss: This results in an increased risk of thrombosis with z. As pulmonary artery embolism, renal vein thrombosis or cerebral venous thrombosis.
albumin loss (+ IgG and ATIII loss): There is a decrease in collo >

Picture: “Plasmodium falciparum nephrosis edema”. License: Public Domain

In the advanced stage can one renal insufficiency arise with corresponding symptoms.

Diagnosis of nephrotic syndrome

The clinical presentation and especially the laboratory tests are the basis of the diagnosis. The Serum electrophoresis shows characteristically a loss of albumin and gamma fraction with relative increase in alpha2 and beta fraction. For further clarification should a sonography kidney. The gold standard of diagnosis, also with regard to the adequate therapy, lies in the renal biopsy and histological evaluation of the glomeruli.

Therapy of nephrotic syndrome

For a systemic cause, a possible therapy should be sought. For inflammatory causes glucocorticoids or even increased immunosuppressive Measures (ciclosporin, cyclophosphamide) use.

Generally, a physical sparing with protein and low-salt diet is recommended. The edema may be gently flushed out. This is necessarily on a balance of electrolytes to pay attention.

Furthermore, the increased needs Thrombophilieneigung thoughtfully and with one thromboprophylaxis be treated prophylactically. For thromboembolic complications must be an effective oral anticoagulation take place because of the antithrombin III deficiency heparin therapy has become apparently ineffective.

Sources and guideline on glomerulonephritis

Herold, G. and co-workers: Internal Medicine (2014) – Gerd Herold Verlag

Floege, A. and Floege, J .: KDIGO guidelines for the treatment of glomerulonephritis published in The Nephrologist, July 2013, Volume 8, Issue 4, pp 327-335

Pavenstädt, H .: Membranous gomerulonephritis published in The Nephrologist, 2011, 6: 220-230

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